Successful Treatment With Lorlatinib Monotherapy for Secondary Central Nervous System Oligometastatic Disease in Refractory Anaplastic Lymphoma Kinase Positive Non-small Cell Lung Cancer.

The anaplastic lymphoma kinase (ALK) gene plays crucial roles in both normal brain development and oncogenesis, particularly in non-small cell lung cancer (NSCLC). Metastatic ALK-positive NSCLC is characterized by ALK tyrosine kinase domain rearrangements, prompting the use of ALK tyrosine kinase inhibitors (TKIs) to target the mutation. While first-line treatment options include alectinib, brigatinib, and lorlatinib per National Comprehensive Cancer Network (NCCN) guidelines, therapeutic challenges arise in cases of disease progression.

Transducer module apodization to reduce bone heating during focused ultrasound uterine fibroid ablation with phased arrays: A numerical study.

Background: During magnetic resonance-guided focused ultrasound (MRgFUS) surgery for uterine fibroids, ablation of fibrous tissues in proximity to the hips and spine is challenging due to heating within the bone that can cause patients to experience pain and potentially damage nerves. This far-field bone heating limits the volume of fibroid tissue that is treatable via MRgFUS.

Purpose: To investigate transducer module apodization for improving the ratio of focal-to-bone heating ( ) when targeting fibroid tissue close to the hips and spine, to enable MRgFUS treatments closer to the bone.

A Transmit-Receive Phased Array for Microbubble-Mediated Focused Ultrasound Brain Therapy in Small Animals.

Unlabelled: Focused ultrasound (FUS) combined with circulating microbubbles (MBs) can be employed for non-invasive, localized agent delivery across the blood-brain barrier (BBB). Previous work has demonstrated the feasibility of clinical-scale transmit-receive phased arrays for performing transcranial therapies under MB imaging feedback.

Objective: This study aimed to design, construct, and evaluate a dual-mode phased array for MB-mediated FUS brain therapy in small animals.

The therapeutic potential of immunoengineering for systemic autoimmunity.

Disease-modifying drugs have transformed the treatment options for many systemic autoimmune diseases. However, an evolving understanding of disease mechanisms, which might vary between individuals, is paving the way for the development of novel agents that operate in a patient-tailored manner through immunophenotypic regulation of disease-relevant cells and the microenvironment of affected tissue domains. Immunoengineering is a field that is focused on the application of engineering principles to the modulation of the immune system, and it could enable future personalized and immunoregulatory therapies for rheumatic diseases.

Immunomodulatory Nanoparticles for Modulating Arthritis Flares.

Disease-modifying drugs have improved the treatment for autoimmune joint disorders, such as rheumatoid arthritis, but inflammatory flares are a common experience. This work reports the development and application of flare-modulating poly(lactic--glycolic acid)-poly(ethylene glycol)-maleimide (PLGA-PEG-MAL)-based nanoparticles conjugated with joint-relevant peptide antigens, aggrecan and type 2 bovine collagen. Peptide-conjugated PLGA-PEG-MAL nanoparticles encapsulated calcitriol, which acted as an immunoregulatory agent, and were termed calcitriol-loaded nanoparticles (CLNP).

Three-dimensional super resolution ultrasound imaging with a multi-frequency hemispherical phased array.

Background: High resolution imaging of the microvasculature plays an important role in both diagnostic and therapeutic applications in the brain. However, ultrasound pulse-echo sonography imaging the brain vasculatures has been limited to narrow acoustic windows and low frequencies due to the distortion of the skull bone, which sacrifices axial resolution since it is pulse length dependent.

Purpose: To overcome the detect limit, a large aperture 256-module sparse hemispherical transmit/receive array was used to visualize the acoustic emissions of ultrasound-vaporized lipid-coated decafluorobutane nanodroplets flowing through tube phantoms and within rabbit cerebral vasculature in vivo via passive acoustic mapping and super resolution techniques.

Cavitation Feedback Control of Focused Ultrasound Blood-Brain Barrier Opening for Drug Delivery in Patients with Parkinson's Disease.

Magnetic resonance-guided focused ultrasound (MRgFUS), in conjunction with circulating microbubbles, is an emerging technology that can transiently enhance the permeability of the blood-brain barrier (BBB) locally and non-invasively to facilitate targeted drug delivery to the brain. In this clinical trial, the feasibility and safety of BBB modulation in the putamen were evaluated for biweekly therapeutic agent delivery in patients with Parkinson's disease. The performance of the clinical MRgFUS system's cavitation feedback controller for active power modulation throughout the exposures was examined.

Putaminal Recombinant Glucocerebrosidase Delivery with Magnetic Resonance-Guided Focused Ultrasound in Parkinson's Disease: A Phase I Study.

Background: GBA1 mutation is the most common genetic risk factor for Parkinson's disease (PD). Replacement of the lysosomal enzyme glucocerebrosidase (GCase) slows neurodegeneration in PD models and may be a promising disease-modifying therapy in patients with PD. However, recombinant GCase has limited penetration through the blood-brain barrier (BBB).

Pediatric Ventilation Liberation: Bundled Extubation Readiness and Analgosedation Pathways Decrease Mechanical Ventilation Duration and Benzodiazepine Exposure.

Background: Recent studies reported that children on mechanical ventilation who were managed with an analgosedation approach and standardized extubation readiness testing experienced better outcomes, including decreased delirium and invasive mechanical ventilation duration.

Methods: This was a quality improvement project in a 24-bed pediatric ICU within a single center, including subjects ≤ 18 years old who required invasive mechanical ventilation via an oral or nasal endotracheal tube. The aim was to decrease the invasive mechanical ventilation duration for all the subjects by 25% within 9 months through the development and implementation of bundled benzodiazepine-sparing analgosedation and extubation readiness testing clinical pathways.

Pediatric ventilation liberation: evaluating the role of endotracheal secretions in an extubation readiness bundle.

Background: An evidence gap exists regarding the role of endotracheal secretions in pediatric extubation decisions. This study aims to evaluate whether endotracheal secretion burden independently correlates with pediatric extubation failure.

Methods: This is a single-center, prospective cohort study of children aged <19 years requiring intubation.

Predicting surface abundance of federally threatened Jollyville Plateau Salamanders () to inform management activities at a highly modified urban spring.

Urban expansion has contributed to the loss of habitat for range restricted species across the globe. Managing wildlife populations within these urban settings presents the challenge of balancing human and wildlife needs. Jollyville Plateau Salamanders () are a range restricted, federally threatened, species of neotenic brook salamander endemic to central Texas.

An Acoustic Measurement Library for Non-Invasive Trans-Rodent Skull Ultrasonic Focusing at High Frequency.

Objective: To investigate the feasibility of developing an acoustic measurement library for non-invasive trans-rodent skull ultrasonic focusing at high frequency.

Methods: A fiber-optic hydrophone (FOH) was positioned at the geometric focus of a spherically-curved phased array (64 elements, 25 mm diameter, 20 mm radius of curvature). Elements were driven sequentially (3.

An Ultrasound-Guided Hemispherical Phased Array for Microbubble-Mediated Ultrasound Therapy.

Goal: To develop a low-cost magnetic resonance imaging (MRI)-free transcranial focused ultrasound (FUS) system for microbubble-mediated therapy.

Methods: A 128-element 11 MHz array for skull localization was integrated within a 256-module multi-frequency (306/612/1224 kHz) dual-mode phased array. The system's transcranial transmit and receive performance was evaluated with ex-vivo human skullcaps using phase aberration corrections calculated from computed tomography (CT)-based simulations via ultrasound-based (USCT) and landmark-based (LMCT) registrations, and a gold-standard fixed source emitter (FSE)-based method.

Implementation of a Skull-Conformal Phased Array for Transcranial Focused Ultrasound Therapy.

Objective: To implement a skull-conformal phased array for ultrasound-guided transcranial focused ultrasound therapy with improved patient comfort.

Methods: Using patient-specific computed tomography and MRI neuroimaging data, tightly-conforming helmet scaffolds were designed computationally. The helmet scaffolds were designed to hold reusable transducer modules at near-normal incidence in an optimal configuration for the treatment location(s) of interest.

Challenging Convention: Daytime Versus Nighttime Extubation in the Pediatric ICU.

Background: The majority of pediatric extubations occur during day shift hours. There is a time-dependent relationship between mechanical ventilation duration and complications. It is not known if extubation shift (day vs night) correlates with pediatric extubation outcomes.

Technical Principles and Clinical Workflow of Transcranial MR-Guided Focused Ultrasound.

Transcranial MR-guided focused ultrasound (MRgFUS) is a rapidly developing technology in neuroscience for manipulating brain structure and function without open surgery. The effectiveness of transcranial MRgFUS for thermoablation is well established, and the technique is actively employed worldwide for movement disorders including essential tremor. A growing number of centers are also investigating the potential of microbubble-mediated focused ultrasound-induced opening of the blood-brain barrier (BBB) for targeted drug delivery to the brain.

Technical and radiographic considerations for magnetic resonance imaging-guided focused ultrasound capsulotomy.

Objective: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is an emerging treatment modality that enables incisionless ablative neurosurgical procedures. Bilateral MRgFUS capsulotomy has recently been demonstrated to be safe and effective in treating obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Preliminary evidence has suggested that bilateral MRgFUS capsulotomy can present increased difficulties in reaching lesional temperatures as compared to unilateral thalamotomy.

Echo-Focusing in Transcranial Focused Ultrasound Thalamotomy for Essential Tremor: A Feasibility Study.

Background: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) systems currently employ computed tomography (CT)-based aberration corrections, which may provide suboptimal trans-skull focusing.

Objectives: The objective of this study was to evaluate a contrast agent microbubble imaging-based transcranial focusing method, echo-focusing (EF), during TcMRgFUS for essential tremor.

Methods: A clinical trial of TcMRgFUS thalamotomy using EF for the treatment of essential tremor was conducted (NCT03935581; funded by InSightec [Tirat Carmel, Israel]).

A High-Frequency Phased Array System for Transcranial Ultrasound Delivery in Small Animals.

Existing systems for applying transcranial focused ultrasound (FUS) in small animals produce large focal volumes relative to the size of cerebral structures available for interrogation. The use of high ultrasonic frequencies can improve targeting specificity; however, the aberrations induced by rodent calvaria at megahertz frequencies severely distort the acoustic fields produced by single-element focused transducers. Here, we present the design, fabrication, and characterization of a high-frequency phased array system for transcranial FUS delivery in small animals.